Journal article
Transcription factors IRF8 and PU.1 are required for follicular B cell development and BCL6-driven germinal center responses
H Wang, S Jain, P Li, JX Lin, J Oh, C Qi, Y Gao, J Sun, T Sakai, Z Naghashfar, S Abbasi, AL Kovalchuk, S Bolland, SL Nutt, WJ Leonard, HC Morse
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2019
Abstract
The IRF and Ets families of transcription factors regulate the expression of a range of genes involved in immune cell development and function. However, the understanding of the molecular mechanisms of each family member has been limited due to their redundancy and broad effects on multiple lineages of cells. Here, we report that double deletion of floxed Irf8 and Spi1 (encoding PU.1) by Mb1-Cre (designated DKO mice) in the B cell lineage resulted in severe defects in the development of follicular and germinal center (GC) B cells. Class-switch recombination and antibody affinity maturation were also compromised in DKO mice. RNA-seq (sequencing) and ChIP-seq analyses revealed distinct IRF8 an..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank Alfonso Macias and Bethany Scott for managing the mouse colony. This work was supported in part by the Intramural Research Program of the NIH, NIAID (H.W., S.J., C.Q., Y.G., J.S., T.S., Z.N., S.A., A.L.K., S.B., and H.C.M.), and NHLBI (P.L., J.-X.L., J.O., and W.J.L.). S.L.N. was supported by grants from the National Health and Medical Research Council of Australia (1054925, 1058238).